The immune response (I) region of the major histocompatibility complex in the mouse (H-2) has been recently shown to code for what appears to be a distinct class of antigens detectable by serological methods, the so-called I region associated (Ia) antigens. The program proposed in this application is aimed at the serological, genetic and functional analysis of the Ia antigens. The serological analysis will include an extensive series of immunizations, utilizing the resources of the presently available I-congenic strains, as well as strains differing in other H-2 regions, in addition to the I region. The produced antisera will be tested using panels of standard inbred and congenic lines carrying H-2 haplotypes derived by intra-H-2 recombination. The molecular relationships among the individual Ia antigens, as well as between Ia and H-2 antigens will be determined by the method of antibody-induced antigen redistribution (capping). The results of the serological and capping analyses will be used as a basis for interpreting the genetic organization of the I region. Attempts will be made to produce antisera against receptors involved in the cell recognition phase of the various forms of cell-mediated immunity. The combined analysis should provide information to understand the involvement of the I region in the genetic control of disease susceptibility.